Fortunately, recent targeted as well as unbiased proteomic profiling studies have identified several promising urinary biomarkers

Fortunately, recent targeted as well as unbiased proteomic profiling studies have identified several promising urinary biomarkers. in additional large prospective studies, the RAIL biomarkers will transform the care of patients with LN, allowing for a personalized and predictive approach and improved outcomes. is a nephroprotective protein that is induced very early after injury in renal epithelial cells in the distal and collecting nephron segments, from where it is rapidly secreted into the urine. It has been successfully utilized as a non-invasive biomarker for acute kidney injuries in a wide number of studies [37]. NGAL protein is also well known to be induced and over-expressed in kidney tubule cells in human LN. Brunner et al. [38] explored the utility of urinary NGAL as a biomarker in pediatric LN. In a cross-sectional assessment of 35 SLE patients (17 of which had biopsy-proven LN), urinary NGAL levels were significantly higher in LN patients compared to children with lupus that did not have LN, and to disease controls with juvenile arthritis. NGAL levels correlated strongly with LN activity as measured by the renal domain score of the Systemic Lupus Disease Activity Index (SLEDAI) and with LN damage as measured by the Systemic Lupus Collaborating Clinics (SLICC) damage index scores. Conversely, urine NGAL levels were not associated with extra-renal SLEDAI scores. At a cut-off value of 0.6 ng/mg urinary creatinine, urinary NGAL was 90% sensitive and RIPK1-IN-3 100% specific in identifying LN patients [38]. The ability of urinary NGAL to differentiate between LN and non-LN patients with a RIPK1-IN-3 high degree of sensitivity and specificity has been recently confirmed in other cohorts with different patient ethnicities [39,40]. In a subsequent longitudinal study by Brunner et al., urinary NGAL levels were associated with worsening renal disease in SLE patients. Urinary NGAL discriminates between WHO class IV and class V LN in a subset of patients with biopsies within 2 months of the urine samples used to measure NGAL [41]. With regards to ability to predict a flare, urinary NGAL levels showed significant increase up to 3 months prior to LN flare [42]. Conversely, Kiani et al. reported the lack of association between urinary NGAL and measures of LN in a study of 107 SLE patients [43]. However, the majority of studies that utilized this marker reported its usefulness in predicting LN RIPK1-IN-3 activity, flares, and worsening renal disease [38C42], rendering it a desirable target in this field. 4.2. RIPK1-IN-3 Monocyte chemoattractant protein-1 (MCP-1) is a member of the family of chemokines regulating the migration and infiltration of inflammatory cells to target tissues [44]. The association of this chemokine with the development of LN has stimulated the study of its urinary excretion and implications for LN [45,46]. Urinary MCP-1 was found to be significantly elevated with active LN as compared to inactive LN, to extra-renal lupus activity, or to healthy controls [47,48]. The levels of urinary MCP-1 decrease with high dose intravenous steroids use to levels that are comparable to MCP-1 levels of healthy control urines. Likewise low urine MCP-1 levels are present during remission of LN [47]. Over time, urinary MCP-1 levels decrease significantly with anti-inflammatory therapy and are correlated with renal SLEDAI scores [49]. Rovin et al. demonstrated an elevation of urinary MCP-1 in LN patients starting 2 and 4 months prior to LN flares, a decrease in urinary MCP-1 levels upon improvement of LN activity and continuously high MCP-1 levels in non-responders to LN therapy [50]. Collectively, these findings support the usefulness of urinary MCP-1 as a predictor for LN activity, flares, recovery, and response to treatment. Cross-sectional baseline levels of urinary RIPK1-IN-3 MCP-1 in LN patients also demonstrated significant associations with the Rabbit Polyclonal to IRF-3 (phospho-Ser386) histological class of LN (= 0.036), with the highest levels present in class IV LN [51]. 4.3. Vascular cellular adhesion molecule-1 (VCAM-1) is an adhesion molecule that mediates the adherence of inflammatory cells to target cells in the kidney [52]. Abd-Elkareem et al. [53] demonstrated that urinary VCAM-1 levels can help discriminate between histological classes of LN with the higher levels observed with WHO class III, IV and V LN compared to class I, II and non-LN patients. Urinary VCAM-1 levels may be associated with LN histologic activity index in urine samples obtained at the time of the biopsy [54]. Urinary VCAM-1 levels were found to correlate with renal damage as measured by the renal domain score of the SLICC damage index and with the degree of.